Ji, Yan, Calonder, Claudio, Kirsilae, Tiina, Joubert, Yolandi, Laurent, Nathalie, Hua, Eva, Patekar, Manmath, Drollmann, Anton Franz and Woessner, Ralph (2023) Comprehensive assessment of pharmacokinetics, pharmacodynamics and tolerability of ligelizumab in healthy volunteers and patients with chronic spontaneous urticaria to optimize its subcutaneous delivery system. Pharmaceutics, 15 (9). p. 2266. ISSN 1999-4923

Abstract

Ligelizumab is a highly potent, humanized IgG1 anti-IgE monoclonal antibody. To explore its opti-mal subcutaneous delivery, pharmacokinetics (PK), pharmacodynamics (PD), and tolerability of ligelizumab from two Phase 1 studies in healthy volunteers (HVs) and four Phase 2 and 3 studies in patients with chronic spontaneous urticaria (CSU) were assessed. Using different in-jection volume or duration of liquid-in-vial (LIVI) formulation or different formulations [LIVI vs. pre-filled syringe (PFS)], single-dose ligelizumab showed comparable PK exposure in HVs. Steady-state exposure of ligelizumab was also comparable between LIVI and PFS following mul-tiple dosing in CSU patients. Total IgE level (PD marker) and tolerability were similar between the two formulations in both HVs and patients. Furthermore, PK, total IgE and tolerability were comparable for PFS administered ei-ther by patients or health care providers (HCPs). Collective evidence demonstrated that injection duration or volume, formulation, or administrator had no apparent impact on PK, PD and tolerabil-ity of ligelizumab, supporting no clinically relevant difference between that LIVI and PFS of ligelizumab and PFS can be administered by patients or HCP. This report provides a comprehensive assessment based on data of multiple clinical endpoints from both HVs and patients to inform formulation develop-ment and commercial use of a monoclonal antibody.

Item Type:	Article
Date Deposited:	19 Mar 2024 00:45
Last Modified:	19 Mar 2024 00:45
URI:	https://oak.novartis.com/id/eprint/51403